Growth inhibitory effects of dihydroartemisinin on pancreatic cancer cells: involvement of cell cycle arrest and inactivation of nuclear factor-kappaB

J Cancer Res Clin Oncol. 2010 Jun;136(6):897-903. doi: 10.1007/s00432-009-0731-0. Epub 2009 Nov 26.


Purpose: In a recent publication, we have shown that dihydroartemisinin (DHA), a derivative of antimalaria drug artemisinin, inhibits growth of pancreatic cancer cells in vitro and in vivo mediated by its anti-proliferative and pro-apoptotic effects. As it has been shown that the apoptosis might be induced due to cell cycle arrest, and that transcriptional factor nuclear factor-kappa B (NF-kappaB) plays vital roles in the apoptosis of pancreatic cancer cells, we extend our study to investigate the effects of DHA on cell cycle progression and NF-kappaB activity in pancreatic cancer cells to further reveal the anticancer effects of DHA on pancreatic cancer.

Methods: Cell cycle progression was determined by propidium iodide staining and flow cytometry. Changes in the expression of cell cycle-associated proteins were detected using Western blot analysis. Measurement of NF-kappaB activity was performed with immunoblot analyzing the nuclear protein expression of NF-kappaB/p65 and ELISA detecting the NF-kappaB DNA-binding activity.

Results: The treatment with DHA resulted in a dose-dependent G(0)/G(1) cell cycle arrest and regulated the expression of some cyclins, cdks and cdk inhibitors that involved in the G(0)/G(1) cell cycle progression such as cyclin E, cdk2, cdk4 and p27(Kip1) in pancreatic cancer BxPC-3 and AsPC-1 cells. The translocation and DNA-binding activity of NF-kappaB were inhibited in DHA-treated cells in a dose-dependent manner, indicated the inactivation effects of DHA in pancreatic cancer cells.

Conclusions: Together with our previous observations, our data show that DHA induces cell cycle arrest and apoptosis in pancreatic cancer cells, and this effect might be due to inhibition of NF-kappaB signaling. We suggest that DHA could be developed as a novel agent against pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Artemisinins / pharmacology*
  • Blotting, Western
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interphase / drug effects
  • NF-kappa B / antagonists & inhibitors*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Translocation, Genetic / drug effects


  • Antineoplastic Agents
  • Artemisinins
  • NF-kappa B
  • artenimol